Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma

Zihuang Li,1 Ling Ye,2 Jingwen Liu,1 Daizheng Lian,1 Xianming Li1 1Department of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of China; 2Department of Oncology, The First Affi...

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Autores principales:	Li Z, Ye L, Liu J, Lian D, Li X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	dendritic block copolymer sorafenib enhanced therapy tpgs hepatocellular carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/da92be5c059e4130a8a5548c3a7a62b8
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spelling	oai:doaj.org-article:da92be5c059e4130a8a5548c3a7a62b82021-12-02T09:30:59ZSorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma1178-2013https://doaj.org/article/da92be5c059e4130a8a5548c3a7a62b82020-03-01T00:00:00Zhttps://www.dovepress.com/sorafenib-loaded-nanoparticles-based-on-biodegradable-dendritic-polyme-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zihuang Li,1 Ling Ye,2 Jingwen Liu,1 Daizheng Lian,1 Xianming Li1 1Department of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Zihuang Li; Xianming LiDepartment of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of ChinaTel +86 755 22942428Email li.zihuang@szhospital.com; li.xianming@szhospital.comPurpose: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC.Methods: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS).Results: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects.Conclusion: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.Keywords: dendritic block copolymer, sorafenib, enhanced therapy, TPGS, hepatocellular carcinomaLi ZYe LLiu JLian DLi XDove Medical Pressarticledendritic block copolymersorafenibenhanced therapytpgshepatocellular carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1469-1480 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	dendritic block copolymer sorafenib enhanced therapy tpgs hepatocellular carcinoma Medicine (General) R5-920
spellingShingle	dendritic block copolymer sorafenib enhanced therapy tpgs hepatocellular carcinoma Medicine (General) R5-920 Li Z Ye L Liu J Lian D Li X Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma
description	Zihuang Li,1 Ling Ye,2 Jingwen Liu,1 Daizheng Lian,1 Xianming Li1 1Department of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Zihuang Li; Xianming LiDepartment of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of ChinaTel +86 755 22942428Email li.zihuang@szhospital.com; li.xianming@szhospital.comPurpose: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC.Methods: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS).Results: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects.Conclusion: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.Keywords: dendritic block copolymer, sorafenib, enhanced therapy, TPGS, hepatocellular carcinoma
format	article
author	Li Z Ye L Liu J Lian D Li X
author_facet	Li Z Ye L Liu J Lian D Li X
author_sort	Li Z
title	Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma
title_short	Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma
title_full	Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma
title_fullStr	Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma
title_full_unstemmed	Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma
title_sort	sorafenib-loaded nanoparticles based on biodegradable dendritic polymers for enhanced therapy of hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/da92be5c059e4130a8a5548c3a7a62b8
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Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma

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